RESUMO
A preponderance of recent evidence indicates that oxybenzone and other personal-care product chemicals threaten the biota inhabiting various ecological niches. What is understudied is the ecotoxicological impact of oxybenzone, a UV filter in sunscreens and anti-aging products, to terrestrial/soil organisms that are keystone species in these habitats. In the present study, acute exposure (14-day) to oxybenzone resulted in earthworm mortality (LC50 of 364 mg/kg) and growth rate inhibition. Environmentally relevant concentration of oxybenzone (3.64, 7.28 and 36.4 mg/kg) at exposures of 7-day, 14-day, 28-day induced oxidative stress and neurotoxicity followed by perturbations in reproduction processes and changes in vital organs. Decreased levels of superoxide dismutase (SOD) and catalase (CAT) activity were statistically lower than controls (p < 0.05) on day 14 for all three concentrations, while glutathione-s-transferase (GST) activity was significantly elevated from controls on days 7 and 14. On day 28, SOD and CAT activities were either not significantly different from the control or were higher, demonstrating a temporal multiphasic response of anti-oxidant enzymes. GST activity on day 28 was significantly reduced compared to controls. Acetylcholinesterase levels across the three-time points exhibited a complicated behaviour, with every exposure concentration being significantly different from the control. Chronic exposure negatively influences earthworm health status with elevated biomarker values analysed using IBRv2 index. This, in turn, impacted higher levels of hierarchical organization, significantly impairing reproduction and organismal homeostasis at the histological level and manifesting as decreasing cocoon formation and successful hatching events. Thus, the overall findings demonstrate that oxybenzone is toxic to Eisenia fetida at low-level, long-term exposure. Based on the concentration verification analysis and application of the EPA PestDF tool, oxybenzone undergoes single first-order kinetics degradation in OECD soil with DT50 and DT90 as 8.7-28.9 days, respectively.
Assuntos
Oligoquetos , Poluentes do Solo , Acetilcolinesterase/metabolismo , Animais , Antioxidantes/metabolismo , Benzofenonas , Catalase/metabolismo , Oligoquetos/metabolismo , Estresse Oxidativo , Solo/química , Poluentes do Solo/metabolismo , Poluentes do Solo/toxicidade , Superóxido Dismutase/metabolismoRESUMO
Benzophenone is a mutagen, carcinogen, and endocrine disruptor. Its presence in food products or food packaging is banned in the United States. Under California Proposition 65, there is no safe harbor for benzophenone in any personal care products, including sunscreens, anti-aging creams, and moisturizers. The purpose of this study was to determine (1) if benzophenone was present in a wide variety of commercial sun protection factor (SPF)/sunscreen products, (2) whether benzophenone concentration in the product increased over time, and (3) if the degradation of octocrylene was the likely source for benzophenone contamination. Benzophenone concentration was assayed in nine commercial sunscreen products from the European Union and eight from the United States (in triplicate), including two single ingredient sources of octocrylene. These same SPF items were subjected to the United States Food and Drug Administration (U.S. FDA)-accelerated stability aging protocol for 6 weeks. Benzophenone was measured in the accelerated-aged products. Sixteen octocrylene-containing product lines that were recently purchased had an average concentration of 39 mg/kg benzophenone, ranging from 6 mg/kg to 186 mg/kg. Benzophenone was not detectable in the product that did not contain octocrylene. After subjecting the 17 products to the U.S. FDA-accelerated stability method, the 16 octocrylene-containing products had an average concentration of 75 mg/kg, ranging from 9.8 mg/kg to 435 mg/kg. Benzophenone was not detectable in the product that did not contain octocrylene. Benzophenone was detected in the pure octocrylene manufactured ingredient. Octocrylene generates benzophenone through a retro-aldol condensation. In vivo, up to 70% of the benzophenone in these sunscreen products may be absorbed through the skin. U.S. FDA has established a zero tolerance for benzophenone as a food additive. In the United States, there were 2999 SPF products containing octocrylene in 2019. The safety of octocrylene as a benzophenone generator in SPF or any consumer products should be expeditiously reviewed by regulatory agencies.
Assuntos
Acrilatos/metabolismo , Benzofenonas/metabolismo , Protetores Solares/metabolismo , Acrilatos/química , Benzofenonas/química , Contaminação de Alimentos/análise , Humanos , Estrutura Molecular , Protetores Solares/química , Fatores de Tempo , Estados UnidosRESUMO
Most organic ultraviolet filters are very lipophilic and some of them are difficult to quantify in the environment. This article describes an optimization method for the quantification of these compounds in sand samples with diverse compositions. The standard additions method was used. The search for a unique high-performance liquid chromatography method to analyze all these filters along with the search for optimal detection conditions are presented in detail. The best extraction solvent was methanol, and the best conditions for analysis and detection involved the use of a high-performance liquid chromatography system equipped with a biphenyl column (2.6 µm, 150 × 4.6 mm), and an Orbitrap MS detector. We also demonstrated that sample freeze-drying can induce significant loss of some of the ultraviolet filters.
RESUMO
Benzophenone-3 (BP-3; oxybenzone) is an ingredient in sunscreen lotions and personal-care products that protects against the damaging effects of ultraviolet light. Oxybenzone is an emerging contaminant of concern in marine environmentsproduced by swimmers and municipal, residential, and boat/ship wastewater discharges. We examined the effects of oxybenzone on the larval form (planula) of the coral Stylophora pistillata, as well as its toxicity in vitro to coral cells from this and six other coral species. Oxybenzone is a photo-toxicant; adverse effects are exacerbated in the light. Whether in darkness or light, oxybenzone transformed planulae from a motile state to a deformed, sessile condition. Planulae exhibited an increasing rate of coral bleaching in response to increasing concentrations of oxybenzone. Oxybenzone is a genotoxicant to corals, exhibiting a positive relationship between DNA-AP lesions and increasing oxybenzone concentrations. Oxybenzone is a skeletal endocrine disruptor; it induced ossification of the planula, encasing the entire planula in its own skeleton. The LC50 of planulae exposed to oxybenzone in the light for an 8- and 24-h exposure was 3.1 mg/L and 139 µg/L, respectively. The LC50s for oxybenzone in darkness for the same time points were 16.8 mg/L and 779 µg/L. Deformity EC20 levels (24 h) of planulae exposed to oxybenzone were 6.5 µg/L in the light and 10 µg/L in darkness. Coral cell LC50s (4 h, in the light) for 7 different coral species ranges from 8 to 340 µg/L, whereas LC20s (4 h, in the light) for the same species ranges from 0.062 to 8 µg/L. Coral reef contamination of oxybenzone in the U.S. Virgin Islands ranged from 75 µg/L to 1.4 mg/L, whereas Hawaiian sites were contaminated between 0.8 and 19.2 µg/L. Oxybenzone poses a hazard to coral reef conservation and threatens the resiliency of coral reefs to climate change.
Assuntos
Antozoários/efeitos dos fármacos , Benzofenonas/toxicidade , Monitoramento Ambiental , Protetores Solares/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Havaí , Ilhas Virgens AmericanasRESUMO
Benzophenone-2 (BP-2) is an additive to personal-care products and commercial solutions that protects against the damaging effects of ultraviolet light. BP-2 is an "emerging contaminant of concern" that is often released as a pollutant through municipal and boat/ship wastewater discharges and landfill leachates, as well as through residential septic fields and unmanaged cesspits. Although BP-2 may be a contaminant on coral reefs, its environmental toxicity to reefs is unknown. This poses a potential management issue, since BP-2 is a known endocrine disruptor as well as a weak genotoxicant. We examined the effects of BP-2 on the larval form (planula) of the coral, Stylophora pistillata, as well as its toxicity to in vitro coral cells. BP-2 is a photo-toxicant; adverse effects are exacerbated in the light versus in darkness. Whether in darkness or light, BP-2 induced coral planulae to transform from a motile planktonic state to a deformed, sessile condition. Planulae exhibited an increasing rate of coral bleaching in response to increasing concentrations of BP-2. BP-2 is a genotoxicant to corals, exhibiting a strong positive relationship between DNA-AP lesions and increasing BP-2 concentrations. BP-2 exposure in the light induced extensive necrosis in both the epidermis and gastro dermis. In contrast, BP-2 exposure in darkness induced autophagy and autophagic cell death.The LC50 of BP-2 in the light for an 8 and 24 hour exposure was 120 parts per million (ppm) and 165 parts per billion (ppb), respectively. The LC50s for BP-2 in darkness for the same time points were 144 parts per million and 548 parts per billion [corrected].
Assuntos
Antozoários/efeitos dos fármacos , Benzofenonas/toxicidade , Protetores Solares/toxicidade , Raios Ultravioleta , Animais , Recifes de Corais , Filtração , Larva/efeitos dos fármacos , Dose Letal Mediana , Microscopia Eletrônica de Transmissão , Nível de Efeito Adverso não Observado , Análise de Regressão , Testes de ToxicidadeRESUMO
Hanauma Bay is a 101-acre bay created by the partial collapse of a volcanic cone and once supported a vibrant coral reef system. It is the most popular swimming area in the Hawaiian Islands and has been reported to have averaged between 2.8 and 3.5 million visitors a year between the 1980s and the 2010s, with visitors averaging between 3000-4000 a day and peaking around 10,000-13,000 per day. Concentrations of oxybenzone and other common UV filters were measured in subsurface water samples and in sands from the beach-shower areas in Hanauma Bay. Results demonstrate that beach showers also can be a source of sunscreen environmental contamination. Hydrodynamic modeling indicates that oxybenzone contamination within Hanauma Bay's waters could be retained between 14 and 50 h from a single release event period. Focusing on only oxybenzone, two different Hazard and Risk Assessment analyses were conducted to determine the danger of oxybenzone to Hanauma Bay's coral reef system. Results indicate that oxybenzone contamination poses a significant threat to the wildlife of Hanauma Bay. To recover Hanauma Bay's natural resources to a healthy condition and to satisfactorily conserve its coral reef and sea grass habitats, effective tourism management policies need to be implemented that mitigate the threat of sunscreen pollution.
Assuntos
Baías , Protetores Solares , Benzofenonas , Recifes de Corais , Havaí , Protetores Solares/toxicidadeRESUMO
In 2019, sands in nearby runoff streams from public beach showers were sampled on three islands in the State of Hawaii and tested for over 18 different petrochemical UV filters. Beach sands that are directly in the plume discharge of beach showers on three of the islands of Hawaii (Maui, Oahu, Hawai'i) were found to be contaminated with a wide array of petrochemical-based UV-filters that are found in sunscreens. Sands from beach showers across all three islands had a mean concentration of 5619 ng/g of oxybenzone with the highest concentration of 34,518 ng/g of oxybenzone at a beach shower in the Waikiki area of Honolulu. Octocrylene was detected at a majority of the beach shower locations, with a mean concentration of 296.3 ng/g across 13 sampling sites with the highest concentration of 1075 ng/g at the beach shower in Waikiki. Avobenzone, octinoxate, 4-methylbenzylidene camphor and benzophenone-2 were detected, as well as breakdown products of oxybenzone, including benzophenone-1, 2,2'-dihydroxy-4-methoxybenzophenone, and 4-hydroxybenzophenone. Dioxybenzone (DHMB) presented the highest concentration in water (75.4 ng/mL), whereas octocrylene was detected in all water samples. Some of these same target analytes were detected in water samples on coral reefs that are adjacent to the beach showers. Risk assessments for both sand and water samples at a majority of the sampling sites had a Risk Quotient > 1, indicating that these chemicals could pose a serious threat to beach zones and coral reef habitats. There are almost a dozen mitigation options that could be employed to quickly reduce contaminant loads associated with discharges from these beach showers, like those currently being employed (post-study sampling and analysis) in the State of Hawaii, including banning the use of sunscreens using petrochemical-based UV filters or educating tourists before they arrive on the beach.
Assuntos
Protetores Solares , Turismo , Havaí , Areia , Protetores Solares/análise , Água/análiseRESUMO
Benthic marine organisms such as mollusks are often exposed to periodic oxygen deficiency (due to the tidal exposure and/or seasonal expansion of the oxygen-deficient dead zones) and pollution by metals [e.g., cadmium, (Cd)]. These stressors can strongly affect mollusks' survival; however, physiological mechanisms of their combined effects are not fully understood. We studied the effects of Cd exposure on metabolic responses to prolonged anoxia and subsequent recovery in anoxia-tolerant intertidal mollusks Crassostrea virginica (eastern oysters). Anoxia led to an onset of anaerobiosis indicated by accumulation of l-alanine, acetate, and succinate. Prolonged anoxia (for 6 days) caused a decline in the maximum activity of electron transport chain and ADP-stimulated (state 3) oxygen uptake by mitochondria (MO(2)), but no change in the resting (state 4) MO(2) of oyster mitochondria, along with a slight but significant reduction of mitochondrial respiratory control ratio. During reoxygenation, there was a significant overshoot of mitochondrial MO(2) (by up to 70% above the normoxic steady-state values) in control oysters. Mild mitochondrial uncoupling during prolonged shutdown in anoxic tissues and a subsequent strong stimulation of mitochondrial flux during recovery may help to rapidly restore redox status and protect against elevated reactive oxygen species formation in oysters. Exposure to Cd inhibits anaerobic metabolism, abolishes reoxygenation-induced stimulation of mitochondrial MO(2), and leads to oxidative stress (indicated by accumulation of DNA lesions) and a loss of mitochondrial capacity during postanoxic recovery. This may result in increased sensitivity to intermittent hypoxia and anoxia in Cd-exposed mollusks and will have implications for their survival in polluted estuaries and coastal zones.
Assuntos
Cádmio/toxicidade , Crassostrea/efeitos dos fármacos , Crassostrea/metabolismo , Oxigênio/metabolismo , Poluentes da Água/toxicidade , Aminoácidos/metabolismo , Anaerobiose/fisiologia , Animais , Cádmio/farmacologia , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/fisiologia , Ácidos Graxos/metabolismo , Hemolinfa/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Consumo de Oxigênio/efeitos dos fármacos , Consumo de Oxigênio/fisiologia , Poluentes da Água/farmacologiaAssuntos
COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/complicações , Comorbidade , Masculino , Feminino , SARS-CoV-2 , Pessoa de Meia-Idade , Tuberculose/epidemiologia , Coinfecção , Adulto , IdosoRESUMO
BACKGROUND: Hereditary lymphoedema-distichiasis (LD) is an autosomal dominant disorder that classically presents as lymphoedema of the limbs, with variable age of onset, and extra aberrant growth of eyelashes from the Meibomian gland (distichiasis). Other major reported complications include cardiac defects, cleft palate, and extradural cysts. Photophobia, exotropia, ptosis, congenital ectropion, and congenital cataracts are additional eye findings. Recently, we reported that truncating mutations in the forkhead transcription family member FOXC2 resulted in LD in two families. METHODS: The clinical findings in seven additional families with LD, including the original family described by Falls and Kertesz, were determined and mutational analyses were performed. RESULTS: Distichiasis was the most common clinical feature followed by age dependent lymphoedema. There is a wide variation of associated secondary features including tetralogy of Fallot and cleft palate. The mutational analyses identified truncating mutations in all of the families studied (two nonsense, one deletion, three insertion, and one insertion-deletion), which most likely result in haploinsufficiency of FOXC2. CONCLUSIONS: FOXC2 mutations are highly penetrant with variable expressivity which is not explicable by the pattern of mutations.
Assuntos
Proteínas de Ligação a DNA/genética , Pestanas/anormalidades , Linfedema/genética , Fatores de Transcrição/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , DNA/química , DNA/genética , Análise Mutacional de DNA , Saúde da Família , Feminino , Fatores de Transcrição Forkhead , Heterogeneidade Genética , Humanos , Linfedema/patologia , Masculino , Pessoa de Meia-Idade , Mutação , FenótipoRESUMO
Coral reefs within the Florida Keys are disappearing at an alarming rate. Coral cover in the Florida Keys National Marine Sanctuary declined by 38% from 1996 to 2000. In 2000, populations of Montastraea annularis at four sites near Molasses Reef within the Florida Keys National Marine Sanctuary and one reef within Biscayne National Park were sampled on a quarterly basis. Anecdotal observations showed corals at Alina's Reef in Biscayne National Park appeared healthy in March, but experienced an acute loss of coral cover by August. Cellular Diagnostic analysis indicated that Alina's Reef corals were in distress: they had been afflicted with a severe oxidative damaging and protein-denaturing stress that affected both the corals and their symbiotic zooxanthellae. This condition was associated with a significant xenobiotic detoxification response in both species, reflecting probable chemical contaminant exposure. These results demonstrate that applying a Cellular Diagnostic approach can be effective in helping to identify stress and its underlying causes, providing diagnostic and prognostic biomarkers of coral health.
Assuntos
Antozoários/fisiologia , Dinoflagellida/fisiologia , Exposição Ambiental , Monitoramento Ambiental/estatística & dados numéricos , Estresse Fisiológico/fisiopatologia , Poluentes Químicos da Água/toxicidade , Análise de Variância , Animais , Antozoários/efeitos dos fármacos , Biomarcadores/análise , Western Blotting , Dinoflagellida/efeitos dos fármacos , Eletroforese em Gel de Poliacrilamida , Ensaio de Imunoadsorção Enzimática , Florida , Dinâmica PopulacionalRESUMO
We assessed the state of knowledge regarding the effects of large-scale pollution with neonicotinoid insecticides and fipronil on non-target invertebrate species of terrestrial, freshwater and marine environments. A large section of the assessment is dedicated to the state of knowledge on sublethal effects on honeybees (Apis mellifera) because this important pollinator is the most studied non-target invertebrate species. Lepidoptera (butterflies and moths), Lumbricidae (earthworms), Apoidae sensu lato (bumblebees, solitary bees) and the section "other invertebrates" review available studies on the other terrestrial species. The sections on freshwater and marine species are rather short as little is known so far about the impact of neonicotinoid insecticides and fipronil on the diverse invertebrate fauna of these widely exposed habitats. For terrestrial and aquatic invertebrate species, the known effects of neonicotinoid pesticides and fipronil are described ranging from organismal toxicology and behavioural effects to population-level effects. For earthworms, freshwater and marine species, the relation of findings to regulatory risk assessment is described. Neonicotinoid insecticides exhibit very high toxicity to a wide range of invertebrates, particularly insects, and field-realistic exposure is likely to result in both lethal and a broad range of important sublethal impacts. There is a major knowledge gap regarding impacts on the grand majority of invertebrates, many of which perform essential roles enabling healthy ecosystem functioning. The data on the few non-target species on which field tests have been performed are limited by major flaws in the outdated test protocols. Despite large knowledge gaps and uncertainties, enough knowledge exists to conclude that existing levels of pollution with neonicotinoids and fipronil resulting from presently authorized uses frequently exceed the lowest observed adverse effect concentrations and are thus likely to have large-scale and wide ranging negative biological and ecological impacts on a wide range of non-target invertebrates in terrestrial, aquatic, marine and benthic habitats.
Assuntos
Poluentes Ambientais/toxicidade , Inseticidas/toxicidade , Invertebrados/efeitos dos fármacos , Agonistas Nicotínicos/toxicidade , Pirazóis/toxicidade , Animais , Ecossistema , Polinização , Medição de RiscoRESUMO
Functional inactivation of the mitochondrial small heat-shock protein (lmw Hsp) in submitochondrial vesicles using protein-specific antibodies indicated that this protein protects NADH:ubiquinone oxidoreductase (complex I), and consequently electron transport from complex I to cytochrome c:O2 oxidoreductase (complex IV). Lmw Hsp function completely accounted for heat acclimation of complex I electron transport in pre-heat-stressed plants. Addition of purified lmw Hsp to submitochondrial vesicles lacking this Hsp increased complex I electron transport rates 100% in submitochondrial vesicles assayed at high temperatures. These results indicate that production of the mitochondrial lmw Hsp is an important adaptation to heat stress in plants.
Assuntos
Frutas/metabolismo , Proteínas de Choque Térmico/fisiologia , Temperatura Alta , NAD(P)H Desidrogenase (Quinona)/metabolismo , Proteínas de Plantas/fisiologia , Transporte de Elétrons/fisiologia , Proteínas de Choque Térmico/isolamento & purificação , Proteínas de Choque Térmico/farmacologia , Mitocôndrias/metabolismo , Complexos Multienzimáticos/metabolismo , NADH NADPH Oxirredutases/metabolismo , Fosforilação Oxidativa , Proteínas de Plantas/isolamento & purificação , Proteínas de Plantas/farmacologiaRESUMO
During the past two decades, coral reefs have experienced extensive degradation worldwide. One etiology for this global degradation is a syndrome known as coral bleaching. Mass coral bleaching events are correlated with increased sea-surface temperatures, however, the cellular mechanism underlying this phenomenon is uncertain. To determine if oxidative stress plays a mechanistic role in the process of sea-surface temperature-related coral bleaching, we examined corals along a depth transect in the Florida Keys over a single season that was characterized by unusually high sea-surface temperatures. We observed strong positive correlations between accumulation of oxidative damage products and bleaching in corals over a year of sampling. High levels of antioxidant enzymes and small heat-shock proteins were negatively correlated with levels of oxidative damage products. Corals that experienced oxidative stress had higher chaperonin levels and protein turnover activity. Our results indicate that coral bleaching is tightly coupled to the antioxidant and cellular stress capacity of the symbiotic coral, supporting the mechanistic model that coral bleaching (zooxanthellae loss) may be a final strategy to defend corals from oxidative stress.
Assuntos
Antozoários/metabolismo , Estresse Oxidativo , Animais , Oceano Atlântico , Chaperoninas/metabolismo , Citosol/metabolismo , Dinoflagellida/metabolismo , Ecologia , Glutationa/metabolismo , Proteínas de Choque Térmico/metabolismo , Peróxido de Hidrogênio/metabolismo , Modelos Biológicos , Espécies Reativas de Oxigênio , Água do Mar , Superóxido Dismutase/metabolismo , Simbiose , TemperaturaRESUMO
PURPOSE: The aim of this study was to screen affected members of glaucoma families for mutations in the Trabecular Meshwork Inducible Glucocorticoid Response (TIGR) gene also known by the name myocilin (MYOC) or by combined names such as TIGR/MYOC. Our primary objectives were (1) to identify mutations responsible for glaucoma in members of three families for which we have shown linkage between chromosome 1 GLC1A-region markers and the primary open angle glaucoma (POAG) phenotype, and (2) to determine the relationship of these and other mutations to key points of predicted function and structure of the TIGR/MYOC protein. METHODS: DNA sequence determination was used to identify sequence changes in sections of the TIGR/MYOC gene that were PCR-amplified from genomic DNA from the probands of three previously-reported GLC1A juvenile-onset POAG families, UM:JG1, UM:JG3, UM:GL57, and unmapped family UM:JG5. Allele-specific oligonucleotide hybridization was used to screen for the identified mutations in PCR-amplified DNA from individual members of each pedigree and from a panel of 11 additional juvenile glaucoma family probands, 42 adult POAG family probands, and 43 normal individuals. Computerized algorithms were used to identify functional motifs and predict structures of normal and mutant forms of the protein. RESULTS: Sequence changes were found that alter amino acids in the olfactomedin-like domain near the carboxy terminal end of the TIGR protein in affected members of families UM:JG1 (Pro370Leu), UM:JG3 (Val426Phe), UM:GL57 (Glu323Lys) and UM:JG5 (Gly252Arg). Co-segregation of glaucoma and Pro370Leu, Val426Phe, and Gly252Arg in known GLC1A families suggests that these are mutations. Although the Gly252Arg substitution observed in UM:JG5 is non-conservative, it was not possible to distinguish whether it is a mutation or a polymorphism. None of the sequence changes described in these families were observed in other juvenile glaucoma cases in this study, nor in any of the POAG or phenotypically normal individuals tested here. Analysis of amino acid sequence changes resulting from mutations described in this and other works demonstrate localization of many mutations in the vicinity of predicted functional motifs in the olfactomedin-like domain. Identification of rat latrophilin (LPH1/CIRL) as a new member of the olfactomedin-like protein family to which TIGR/MYOC belongs suggests that the region of olfactomedin homology is a protein domain that can occur in different protein contexts. CONCLUSIONS: Location of mutations described in this and previous work suggests that some specific predicted protein motifs in the olfactomedin-like domain may be important to TIGR/MYOC function. In some cases, the role of TIGR/MYOC in the etiology of glaucoma may result from alteration of the sequences recognized by modifying enzymes such as casein kinase II. In other cases altered protein folding may affect access of enzymes to their target sequences on TIGR/MYOC. Although modifications and structures discussed here are predicted rather than proven, they provide a useful theoretical framework for design of subsequent experiments. Alterations to protein folding and predicted modification motifs cannot explain the pathogenic mechanisms of all of the known TIGR/MYOC glaucoma mutations.
Assuntos
Proteínas do Olho/genética , Glaucoma de Ângulo Aberto/genética , Glicoproteínas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Aminoácidos , Sequência de Bases , Proteínas do Citoesqueleto , Proteínas da Matriz Extracelular/genética , Proteínas do Olho/química , Proteínas do Olho/fisiologia , Feminino , Ligação Genética , Glicoproteínas/química , Glicoproteínas/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Dados de Sequência Molecular , Mutação , Linhagem , Estrutura Secundária de Proteína , Análise de Sequência de DNA , Homologia de Sequência de AminoácidosRESUMO
PURPOSE: To evaluate two families ascertained only for the presence of glaucoma in which both nail-patella syndrome and glaucoma occur in several generations and to determine whether the two diseases are genetically related. METHODS: Ophthalmologic examinations and orthopedic examinations were performed. DNA samples from family members were screened with a microsatellite repeat marker at the argininosuccinate synthetase (ASS) locus at 9q34, and linkage analysis was performed. RESULTS: Six patients with open-angle glaucoma were found among 13 patients with nail-patella syndrome in family UM:47. Seven patients with glaucoma were found among 11 patients with nail-patella syndrome in family UM:65. In both families, all individuals with glaucoma also had nail-patella syndrome. Two-point linkage analysis resulted in a lod score of 2.98 at a recombination fraction of 0.00 for open-angle glaucoma and nail-patella syndrome. CONCLUSIONS: Linkage results presented here provide strong evidence that the orthopedic and nail anomalies in these two families result from the same nail-patella syndrome locus that has been previously linked to markers at 9q34. These data provide indirect evidence for a possible glaucoma locus at 9q34 and do not allow us to distinguish whether the glaucoma is the result of the nail-patella syndrome mutation or whether there is a separate locus responsible for glaucoma in these families. These studies suggest a need for ophthalmologic examination of individuals with nail-patella syndrome.
Assuntos
Glaucoma de Ângulo Aberto/complicações , Glaucoma de Ângulo Aberto/genética , Síndrome da Unha-Patela/complicações , Síndrome da Unha-Patela/genética , Idoso , Idoso de 80 Anos ou mais , Argininossuccinato Sintase/genética , Criança , Pré-Escolar , Mapeamento Cromossômico , Cromossomos Humanos Par 9 , DNA/genética , Feminino , Ligação Genética , Humanos , Escore Lod , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Linhagem , FenótipoRESUMO
PURPOSE: To characterize clinically and genetically autosomal dominant juvenile-onset primary open-angle glaucoma in a Panamanian family. METHODS: Twenty members of a six-generation family underwent ophthalmologic examination and genetic screening with markers near the GLC1A gene on chromosome 1q. RESULTS: Linkage analysis disclosed evidence linking primary open-angle glaucoma in this family to the GLC1A gene on chromosome 1q, with a maximum lod score of 3.75 for marker D1S431 at an estimated recombination fraction of 0.00. CONCLUSIONS: This is the first report of a Panamanian family in which primary open-angle glaucoma is linked to the GLC1A gene on chromosome 1q.
Assuntos
Cromossomos Humanos Par 1/genética , Ligação Genética , Glaucoma de Ângulo Aberto/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Marcadores Genéticos , Glaucoma de Ângulo Aberto/patologia , Humanos , Pressão Intraocular , Escore Lod , Masculino , Pessoa de Meia-Idade , Panamá , Linhagem , Acuidade VisualRESUMO
PURPOSE: To screen a population with primary open-angle glaucoma for mutations in the gene that encodes the trabecular meshwork inducible glucocorticoid response protein (TIGR), also known as myocilin (MYOC). METHODS: Ophthalmologic information was collected for study subjects with primary open-angle glaucoma and their relatives. Mutation screening of 74 primary open-angle glaucoma probands was conducted by sequencing TIGR/MYOC coding sequence and splice sites. RESULTS: In 23 families we detected 13 nonsynonymous sequence changes, nine of which appear to be mutations likely to cause or contribute to primary open-angle glaucoma. Two mutations, Arg272Gly and Ile499Ser, and one nonsynonymous sequence variant, Asn57Asp, are novel. We found mutations in nine of 25 juvenile glaucoma probands (36%) and two of 49 adult-onset glaucoma probands (4%). Age classification of families rather than individual probands revealed mutations in three of nine families with strictly juvenile primary open-angle glaucoma (33%), and no mutations in 39 families with strictly adult-onset primary open-angle glaucoma (0%). In families with mixed-onset primary open-angle glaucoma containing both juvenile primary open-angle glaucoma and adult-onset primary open-angle glaucoma cases, we found mutations in eight of 26 families (31%). CONCLUSIONS: Our data suggest that Gly252Arg, Arg272Gly, Glu323Lys, Gln368STOP, Pro370Leu, Thr377Met, Val426Phe, Ile477Asn, and Ile499Ser are likely to play roles that cause or contribute to the etiology of autosomal dominant primary open-angle glaucoma. Our finding of more TIGR/MYOC mutations in families with mixed-onset primary open-angle glaucoma than in the families with strictly adult-onset primary open-angle glaucoma implies that the presence of relatives with juvenile primary open-angle glaucoma in a family could be used as a basis for identifying a subset of the population with adult-onset primary open-angle glaucoma with higher prevalence of TIGR/MYOC mutations. To address this issue, and to refine estimations of mutation prevalence in these age-defined subpopulations, prospective study of a larger population ascertained entirely through adult-onset primary open-angle glaucoma probands will be needed.
Assuntos
Envelhecimento/genética , Proteínas do Olho/genética , Glaucoma de Ângulo Aberto/genética , Glicoproteínas/genética , Mutação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Proteínas do Citoesqueleto , Análise Mutacional de DNA , Primers do DNA/química , Feminino , Glaucoma de Ângulo Aberto/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Reação em Cadeia da Polimerase , Prevalência , Malha Trabecular/patologiaRESUMO
We developed a molecular biomarker system (MBS) to assess the physiological status of Palaomenetes pugio (grass shrimp) challenged with exposure to heat stress, cadmium, atrazine, and the water-accommodating fraction of either diesel fuel or bunker fuel No. 2. The MBS assayed 9 specific cellular parameters of shrimp that are indicative of a nonstressed or stressed condition: heat-shock protein 60, heat-shock protein 70, alpha B-crystallin homologue, lipid peroxide, total glutathione level, ubiquitin, mitochondrial manganese superoxide dismutase, metallothionein, and cytochrome P-450 2E homologue. Using these 9 parameters, the MBS can distinguish between the responses to each stressor, and to the nonstressed control conditions. The MBS was able to determine the structural integrity of the cell as defined by protein turnover, protein chaperoning, and lipid composition via lipid peroxide levels, and the status of key metabolic processes such as cytoskeletal integrity and glutathione redox potential. This technology aids in the accurate diagnosis of the health of shrimp because the physiological significance of changes of each parameter is well known. This technology is particularly relevant for environmental monitoring because grass shrimp are used as key indicator species in many estuarine ecosystems. Finally, this system is easy to implement, precise, and can be quickly adapted to an automated high-throughput system for mass sample analysis.